SUMMARY: The WNY Center for Research on Flavored Tobacco Products (CRoFT) is focused on the toxicity of flavorings used in tobacco products, with a particular focus on electronic nicotine delivery systems (ENDS). Flavoring chemicals are an essential part of refill solutions used in ENDS products, waterpipe tobacco and flavored cigars. To this end, most projects within CRoFT require data on the contents and/or emissions of flavorings in products. The Product Analysis Core (PAC) will provide timely data on the chemical constituents of products to be tested within the CRoFT and will inform projects about the relative popularity and product variation of particular products and flavors. The underlying goal of the PAC core is to centralize the production of data related to product features that can then feed the CRoFT projects, helping to improve research efficiency. We plan the following three highly integrated Specific Aims: AIM 1: Determine flavorings used and their concentrations in ENDS refill solutions, waterpipe tobacco products and flavored cigars. We propose an approach to the identification and quantitation of flavoring chemicals in tobacco products using GC-MS and GC-Q-TOF-MS methods. The testing of tobacco product will also involve identifying flavoring ingredients that are carcinogenic, mutagenic, respiratory allergens, sensitizers and irritants. We also will determine inter-product and intra-product variability in flavorings and determine intra- and inter-brand variability in flavorings. AIM 2: Determine flavoring yields and inhaled doses from ENDS aerosol and smoke generated from waterpipe tobacco products and flavored cigars. After identification of flavorings in tobacco products in Aim 1, we will measure flavoring yields in aerosol, smoke or vapor generated in laboratory settings using smoking machines. We will also test generated aerosols for potential reaction and thermal breakdown products of flavorings. In order to ensure compliance to the GLP standards, all tests will be done in a fully compliant quality system. AIM 3: Monitoring trends in flavored tobacco product market share using secondary data analysis. In addition to monitoring characteristics of products themselves, we will utilize market scanner data and PATH database to identify the most common flavors in ENDS and other tobacco products and top-selling flavored ENDS brands. Outcomes for Regulatory Science: In addition to providing relevant data for Projects 1-4, we will develop an approach for toxicological risk assessment of flavors that takes into account the type and concentration of flavoring chemicals in the tobacco products and aerosol/smoke/vapor, identification of any potential thermal breakdown and reaction products, and respiratory risk assessment. This approach will contribute to identifying any evidence of inhalation-specific issues that might make a compound unsuitable for use in tobacco products. Results generated by the PAC can help to develop appropriate product standards and implement robust quality management systems for flavorings in tobacco products.